Spinosyn refers to a large family of compounds produced from the fermentation of soil actinomycetes species of Saccharopolyspora. The individual components from the fermentation broth were subsequently given the generic name of spinosyn to connect these compounds with their producing microorganism, Saccharopolyspora spinose. Members of the spinosyn family share a core structure having a polyketide-derived tetracyclic macrolide appended with two saccharides. There are many naturally occurring variants, which exhibit potent insecticidal activities against many commercially significant species that cause extensive damage to crops and other plants. Some of these variants also exhibit activity against important external parasites of livestock, companion animals and humans.
Fermentation of S. spinosa produces a natural mixture containing spinosyn A as the major component and spinosyn D as the minor component and named spinosad. The structure of spinosyn A was determined by NMR, MS, and X-ray analyses and comprises a tetracyclic polyketide aglycone to which is attached a neutral saccharide substituent (2,3,4-tri-O-methyl-α-L-rhamnosyl) on the C-9 hydroxyl group and an aminosugar moiety (β-D-forosaminyl) on the C-17 hydroxyl group. This spinosyn tetracyclic ring system composed of a cis-anti-trans-5,6,5-tricyclic moiety fused to a 12-membered lactone is a unique ring system.
The second most abundant fermentation component is spinosyn D, which is 6-methyl-spinosyn A. Spinosyn D is likely formed by incorporation of propionate instead of acetate at the appropriate stage during polyketide assembly.
Numerous structurally related compounds from various spinosyn fermentations have now been isolated and identified. Their structures fall into several general categories of single-type changes in the aglycone or saccharides of spinosyn A.
Spinosyns have a unique mechanism of action (MOA) involving disruption of nicotinic acetylcholine receptors. When compared with many other insecticides, spinosyns generally show greater selectivity toward target insects and lesser activity against many beneficial predators. Structure-activity relationships (SARs) have been extensively studied, leading to development of a semisynthetic second-generation derivative, spinetoram (Kirst (2010) J. Antibiotics 63:101-111).
Studies to date have concluded that the mechanism(s) by which spinosyn exerts its insecticidal action is different from those of any other known agents, and thus cross-resistance between spinosyn and other agents was initially absent or low. However, as well known for other insecticides, continued usage is likely to exert selective pressures on insects and to eventually provoke resistance.
The unique and highly complex core structure of the spinosyns has provided challenging opportunities for synthesis. Additionally, with the increase of insect resistance, new spinosyn compounds and methods for their synthesis are needed.